The midbrain of a mouse injected with a pathological form of the α-synuclein protein shows a reduction in dopamine markers (green) and developing protein aggregates (red) characteristic of Parkinson’s disease.

Credit: Courtesy of Kelvin Luk/U. Penn. School of Medicine

The midbrain of a mouse injected with a pathological form of the α-synuclein protein shows a reduction in dopamine markers (green) and developing protein aggregates (red) characteristic of Parkinson’s disease.

Researchers explain their discoveries about the pathology of Parkinson’s disease, which may lead to therapies to arrest the propagation of misfolded a-synuclein that causes the most common type of the disease.

Credit: Perelman School of Medicine/U of Pennsylvania

A study lays to rest remaining doubts regarding the causal link between misfolded α-synuclein protein and Parkinson’s disease brain pathologies (Science, DOI: 10.1126/science.1227157). Researchers now have a mouse model for spontaneous (nongenetic) forms of Parkinson’s disease, which account for more than 90% of all cases in humans. Virginia M.-Y. Lee, Kelvin C. Luk, and colleagues at the University of Pennsylvania injected healthy mice with synthetic misfolded α-synuclein. The mice inexorably developed hallmark Parkinson’s symptoms—problems with balance and motor skills—as the misfolded protein propagated through their brains. After about six months, half of the mice’s dopamine-producing cells had been destroyed and characteristic clumps of the protein known as Lewy bodies had formed. The misfolded α-synuclein link to Parkinson’s disease has long been suspected but not proven. In the new study, the researchers not only used healthy mice, but also injected isolated protein, rather than infected brain tissue, to show that the disease is caused solely by the misfolded protein. The group is now studying ways to arrest the propagation of α-synuclein in the brain by using an antibody therapy.